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对半乳糖胺修饰的打断会降低乳腺癌细胞来源的小细胞外囊泡的促转移功能。

Bisecting GlcNAc modification diminishes the pro-metastatic functions of small extracellular vesicles from breast cancer cells.

机构信息

Joint International Research Laboratory of Glycobiology and Medicinal Chemistry College of Life Science Northwest University Xi'an P.R. China.

Department of Breast Surgery The First Affiliated Hospital of Xi'an Jiaotong University Xi'an P.R. China.

出版信息

J Extracell Vesicles. 2020 Oct;10(1):e12005. doi: 10.1002/jev2.12005. Epub 2020 Oct 30.

DOI:10.1002/jev2.12005
PMID:33304474
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7710122/
Abstract

Small extracellular vesicles (sEVs) are enriched in glycoconjugates and display specific glycosignatures. Aberrant expression of surface glycoconjugates is closely correlated with cancer progression and metastasis. The essential functions of glycoconjugates in sEVs are poorly understood. In this study, we observed significantly reduced levels of bisecting GlcNAc in breast cancer. Introduction of bisecting GlcNAc into breast cancer cells altered the bisecting GlcNAc status on sEVs, and sEVs with diverse bisecting GlcNAc showed differing functions on recipient cells. Carcinogenesis and metastasis of recipient cells were enhanced by sEVs with low bisecting GlcNAc, and the pro-metastatic functions of sEVs was diminished by high bisecting GlcNAc modification. We further identified vesicular integrin β1 as a target protein bearing bisecting GlcNAc. Metastasis of recipient cells was strongly suppressed by high bisecting GlcNAc levels on vesicular β1. Our findings demonstrate the important roles of glycoconjugates on sEVs. Modification of sEV glycosylation may contribute to development of novel targets in breast cancer therapy.

摘要

小细胞外囊泡（sEVs）富含糖缀合物，并显示出特定的糖基化特征。表面糖缀合物的异常表达与癌症的进展和转移密切相关。糖缀合物在 sEVs 中的基本功能尚未得到充分了解。在本研究中，我们观察到乳腺癌中双分支 GlcNAc 的水平显著降低。在乳腺癌细胞中引入双分支 GlcNAc 会改变 sEV 上的双分支 GlcNAc 状态，并且具有不同双分支 GlcNAc 的 sEV 对受体细胞具有不同的功能。具有低双分支 GlcNAc 的 sEV 增强了受体细胞的癌变和转移，而高双分支 GlcNAc 修饰则减弱了 sEV 的促转移功能。我们进一步鉴定了带有双分支 GlcNAc 的囊泡整合素 β1 作为靶蛋白。受体细胞的转移被囊泡 β1 上高双分支 GlcNAc 水平强烈抑制。我们的研究结果表明了糖缀合物在 sEVs 中的重要作用。sEV 糖基化的修饰可能有助于开发乳腺癌治疗的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a4/7710122/ecf483908a5e/JEV2-10-e12005-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a4/7710122/8fe6f8381e14/JEV2-10-e12005-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a4/7710122/490d87b59e84/JEV2-10-e12005-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a4/7710122/c76d9737861f/JEV2-10-e12005-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a4/7710122/7c43539858e5/JEV2-10-e12005-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a4/7710122/b2e0eaeb6a74/JEV2-10-e12005-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a4/7710122/510a11b5da54/JEV2-10-e12005-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a4/7710122/7650e8a9aa09/JEV2-10-e12005-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a4/7710122/ecf483908a5e/JEV2-10-e12005-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a4/7710122/8fe6f8381e14/JEV2-10-e12005-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a4/7710122/490d87b59e84/JEV2-10-e12005-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a4/7710122/c76d9737861f/JEV2-10-e12005-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a4/7710122/7c43539858e5/JEV2-10-e12005-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a4/7710122/b2e0eaeb6a74/JEV2-10-e12005-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a4/7710122/510a11b5da54/JEV2-10-e12005-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a4/7710122/7650e8a9aa09/JEV2-10-e12005-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1a4/7710122/ecf483908a5e/JEV2-10-e12005-g008.jpg

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[7]
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引用本文的文献

[1]
Bisecting GlcNAc enhances CD8 T cell-mediated killing of breast cancer by suppressing PD-L1 expression and its binding to PD-1.

Exp Hematol Oncol. 2025-8-4

[2]
Proximity Labeling-Based Identification of MGAT3 Substrates and Revelation of the Tumor-Suppressive Role of Bisecting GlcNAc in Breast Cancer via GLA Degradation.

Cells. 2025-1-12

[3]
MSC-sEVs exacerbate senescence by transferring bisecting GlcNAcylated GPNMB.

Stem Cell Res Ther. 2025-1-23

[4]
Bisecting GlcNAc modification of vesicular GAS6 regulates CAFs activation and breast cancer metastasis.

Cell Commun Signal. 2025-1-22

[5]
Integrin β1 in breast cancer: mechanisms of progression and therapy.

Breast Cancer. 2025-1

[6]
Hypoxia-Induced Adaptations of N-Glycomes and Proteomes in Breast Cancer Cells and Their Secreted Extracellular Vesicles.

Int J Mol Sci. 2024-9-23

[7]
Bisecting GlcNAc modification reverses the chemoresistance via attenuating the function of P-gp.

Theranostics. 2024

[8]
Sialyl Lewis X decorated integrin α3 on small extracellular vesicles promotes metastasis of bladder cancer via enhancing vascular permeability.

Angiogenesis. 2024-11

[9]
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J Extracell Vesicles. 2024-9

[10]
O-GlcNAcylation determines the function of the key O-GalNAc glycosyltransferase C1GalT1 in bladder cancer.

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本文引用的文献

[1]
The Essential Functions and Detection of Bisecting GlcNAc in Cell Biology.

Front Chem. 2020-7-3

[2]
M2 Macrophage-Derived Exosomes Facilitate HCC Metastasis by Transferring α β Integrin to Tumor Cells.

Hepatology. 2021-4

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MGAT3-mediated glycosylation of tetraspanin CD82 at asparagine 157 suppresses ovarian cancer metastasis by inhibiting the integrin signaling pathway.

Theranostics. 2020

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Glycan modification of glioblastoma-derived extracellular vesicles enhances receptor-mediated targeting of dendritic cells.

J Extracell Vesicles. 2019-8-9

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Assessing the role of surface glycans of extracellular vesicles on cellular uptake.

Sci Rep. 2019-8-15

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Bisecting GlcNAc Is a General Suppressor of Terminal Modification of -glycan.

Mol Cell Proteomics. 2019-8-2

[7]
Recognition of Bisecting N-Glycans on Intact Glycopeptides by Two Characteristic Ions in Tandem Mass Spectra.

Anal Chem. 2019-4-22

[8]
Reassessment of Exosome Composition.

Cell. 2019-4-4

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Surface molecules of extracellular vesicles secreted by the helminth pathogen Fasciola hepatica direct their internalisation by host cells.

PLoS Negl Trop Dis. 2019-1-18

[10]
Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models.

Nat Cell Biol. 2018-12-31

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